Efficacy, Safety and Tolerability of VS-01 in Adult Patients With Acute-on-Chronic Liver Failure and Ascites (UNVEIL-IT)®

A Phase 2a, Open-label, Randomized, Controlled, Multi-center Proof of Concept Study to Assess the Efficacy, Safety, and Tolerability of VS-01 on Top of Standard of Care, Compared to Standard of Care Alone, in Adult Patients With Acute-on-chronic Liver Failure (ACLF)

A Phase 2, multi-center, randomized, controlled, open-label study to evaluate the effects of the intraperitoneal, liposomal formulation VS-01 in patients with an acute episode of hepatic and/or extrahepatic organ dysfunctions and failures in the presence of liver cirrhosis (Acute-on-Chronic Liver Failure, ACLF) and accumulation of fluid in the abdominal cavity (ascites)

Study Overview

• Status: Terminated
• Conditions: Acute-On-Chronic Liver Failure; Ascites
• Intervention / Treatment: Drug: VS-01 on top of SOC; Other: SOC (Control Group)

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
• France
  • Chambray-lès-Tours, France, 37170
    • Centre Hospitalier Regional Universitaire de Tours
  • Lyon, France, 69004
    • Hôpital de la Croix Rousse
  • Paris, France, 75013
    • Hôpital Universitaire Pitié Salpêtrière
  • Rennes, France, 35033
    • CHU Rennes - Hôpital Pontchaillou
• Germany
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • North Rhine-Westphalia
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitätsklinikum Münster
  • State of Berlin
    • Berlin, State of Berlin, Germany, 13353
      • Charité Universitätsmedizin Berlin
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Eger, Hungary, 3300
    • Heves Vármegyei Markhot Ferenc Oktatókórház és Rendelőintézet
• Italy
  • Milan, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Roma, Italy, 00185
    • Azienda Ospedaliero-Universitaria Policlinico Umberto I
• Spain
  • Barcelona
    • Barcelona, Barcelona, Spain, 08036
      • Hospital Clinic de Barcelona
• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Health Care
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center/ New York Presbyterian Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75203
      • The Liver Institute at Methodist Dallas
    • Houston, Texas, United States, 77030
      • Baylor Clinic
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23249
      • Richmond VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with ACLF Grade 1, 2, or 3a according to European Association for the Study of the Liver (EASL)-CLIF criteria;
2. Onset of ACLF not more than 14 days before Baseline (BL);
3. Presence of ascites requiring diagnostic or therapeutic paracentesis;
4. Patients with dry body weight ≥40 and <140 kg;
5. Written informed consent obtained prior to the start of any study-related procedures.

Exclusion Criteria:

1. Presence of any of the following organ failure(s) as per the EASL-CLIF criteria and/or adapted from CLIF-C Organ Failure (CLIF-C OF)/CLIF- Sequential Organ Failure Assessment (CLIF-SOFA) scores:

   1. Respiratory failure necessitating invasive mechanical ventilation;
   2. Coagulation failure (INR > 3.2 or platelet count ≤20 x 109/L);
   3. Severe cardiovascular failure requiring the use of high dose vasopressors;
2. ACLF grade 3b: Presence of four or more organ failures as per EASL CLIF criteria;
3. Presence of spontaneous or secondary bacterial peritonitis;
4. Presence of uncontrolled severe infection(with hemodynamic instability or shock);
5. Poorly controlled seizure disorder;
6. Patients with history of upper gastro-intestinal bleeding over the past 7 days prior to BL, acute bleeding or bleeding upon paracentesis at screening (SCR) or BL;
7. Contraindication for paracentesis;
8. Coagulation disorders such as disseminated intravascular coagulation or hemophilia;
9. Potential or known hypersensitivity to liposomes;
10. Potential or known risk factors for allergic/anaphylactoid like reactions (e.g., mastocytosis/elevated basal tryptase) or multiple hypersensitivities;
11. Patients after organ transplantation receiving immunosuppressive medication;
12. Any severe disease considered to be potentially detrimental at the discretion of the Principal Investigator. This includes but is not limited to hepatocellular carcinoma outside Milan criteria, cholangiocarcinoma, extrahepatic cancer over the past 2 years or people who inject drugs;
13. Need for Renal Replacement Therapy or any extracorporeal liver support device (e.g., MARS®, Prometheus®, plasmapheresis);
14. Alfapump® in place to manage ascites;
15. Pregnancy and lactation;
16. Women of child-bearing potential who are not willing to use adequate contraception;
17. Patients who participate in another clinical trial at the time of SCR or within 4 weeks prior to SCR.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VS-01 on top of SOC (Active Treatment Group); Patients randomized to Active Treatment group will receive VS-01 on top of SOC	Drug: VS-01 on top of SOC; Patients will receive VS-01 intraperitoneally on four consecutive days on top of SOC
Other: SOC (Control Group); Patients randomized to Control group will receive SOC defined as the standard medical management of patients with decompensated cirrhosis and ACLF	Other: SOC (Control Group); Patients will receive SOC for decompensated cirrhosis and ACLF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic Liver Failure Consortium (CLIF-C) ACLF Score at Day 7	The CLIF-C ACLF score is derived from the CLIF-C organ failure (OF) score. The formula for the CLIF-C ACLF score is CLIF-ACLF = 10*[0.33*CLIF-C OF + 0.04*Age + 0.63*Ln(white cell count) -2]. The CLIF-C ACLF score ranges from 0-100, where a higher score indicated a greater mortality risk.	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Deaths From Day 1 to Day 90	90-Day mortality was reported as the number of deaths from Day 1 to Day 90.	Day 1 to Day 90
Number of Deaths From Day 1 to Day 28	28-Day mortality was reported as the number of deaths from Day 1 to Day 28.	Day 1 to Day 28
Time to Death Through Day 90	Time to death was calculated as death date - treatment start date. Participants who were not observed to have encountered the event through Day 90 were censored. The inter-quartile range was obtained via Kaplan Meier estimation.	Day 1 to Day 90
Number of Participants With ACLF Resolution	ACLF resolution was defined as ACLF grade 'No ACLF', for participants who had ACLF at Baseline.	Baseline to Day 7 and Day 28
Time to ACLF Resolution Through Day 28	ACLF resolution was defined as ACLF grade 'No ACLF', for participants who had ACLF at Baseline. Time to ACLF resolution was calculated as (ACLF resolution date - treatment start date). Participants who were not observed to have encountered the event through Day 28 were censored at min[trial discontinuation date; Day 28 visit date or treatment start date +27 if no visit date; last contact/assessment date for participant lost to follow-up; date of liver transplant or transjugular intrahepatic portosystemic shunt (TIPS)]. The inter-quartile range was obtained via Kaplan Meier estimation.	Baseline to Day 28
Number of Participants With ≥ 1 ACLF Grade Regression	ACLF regression was defined as regression of at least one full grade.	Baseline, Day 7 and Day 28
Time to ≥ 1 ACLF Grade Regression Through Day 28	Time to ACLF ≥ 1 grade regression was calculated as (ACLF ≥ 1 grade regression date - treatment start date). Participants who were not observed to have encountered the event through Day 28 were censored. The inter-quartile range was obtained via Kaplan Meier estimation.	Baseline and Day 28
Secondary: Time to Transplant or Death Through Day 90	Time to transplant was calculated as (transplant or death date - treatment start date). Participants who were not observed to have encountered the event through Day 90 were censored. The inter-quartile range was obtained via Kaplan Meier estimation.	Day 1 through Day 90
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An AE was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a study drug and that does not necessarily have a causal relationship with this treatment. A TEAE was the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after at least one dose of the study drug had been administered, even if the event was not considered to be related to the study drug. A serious AE (SAE) was any untoward medical event that occurs at any dose that: resulted in death; was life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; or was an important medical event.	Up to Day 90

Collaborators and Investigators

• Sponsor: Genfit
• Investigators: Study Director: Pejvack MOTLAGH, M.D, M.Sc, Genfit

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2023
• Primary Completion (Actual): October 15, 2025
• Study Completion (Actual): October 15, 2025

Study Registration Dates

• First Submitted: June 2, 2023
• First Submitted That Met QC Criteria: June 2, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Cirrhosis; Renal Impairment; Hepatic Impairment; Chronic liver diseases; Liver Failure; Renal Disease; Hepatic Dysfunction; Extrahepatic Organ Dysfunction; Hepatic Decompensation
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Digestive System Diseases; Hepatic Insufficiency; Liver Failure, Acute; Pathological Conditions, Signs and Symptoms; Fibrosis; Liver Diseases; Renal Insufficiency; Kidney Diseases; Liver Failure; Ascites; Acute-On-Chronic Liver Failure; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Control Groups
• Other Study ID Numbers: VS01-IIa-01; 2024-513706-56-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No